Wilson George D, Thibodeau Bryan J, Fortier Laura E, Pruetz Barbara L, Galoforo Sandra, Marples Brian, Baschnagel Andrew M, Akervall Jan, Huang Jiayi
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48703, USA; Beaumont BioBank, William Beaumont Hospital, Royal Oak, MI 48703, USA.
Beaumont BioBank, William Beaumont Hospital, Royal Oak, MI 48703, USA.
Stem Cells Int. 2016;2016:1894782. doi: 10.1155/2016/1894782. Epub 2016 Jan 6.
The aim of the study was to investigate cancer stem signaling during the repopulation response of a head and neck squamous cell cancer (HNSCC) xenograft after radiation treatment. Xenografts were generated from low passage HNSCC cells and were treated with either sham radiation or 15 Gy in one fraction. At different time points, days 0, 3, and 10 for controls and days 4, 7, 12, and 21, after irradiation, 3 tumors per group were harvested for global gene expression, pathway analysis, and immunohistochemical evaluation. 316 genes were identified that were associated with a series of stem cell-related genes and were differentially expressed (p ≤ 0.01 and 1.5-fold) at a minimum of one time point in UT-SCC-14 xenografts after radiation. The largest network of genes that showed significant changes after irradiation was associated with CD44, NOTCH1, and MET. c-MET and ALDH1A3 staining correlated with the changes in gene expression. A clear pattern emerged that was consistent with the growth inhibition data in that genes associated with stem cell pathways were most active at day 7 and day 12 after irradiation. The MET/CD44 axis seemed to be an important component of the repopulation response.
本研究的目的是调查头颈部鳞状细胞癌（HNSCC）异种移植瘤在放射治疗后的再增殖反应过程中的癌症干细胞信号传导。异种移植瘤由低传代HNSCC细胞生成，分别接受假放射治疗或单次15 Gy照射。在不同时间点，对照组为第0、3和10天，照射后为第4、7、12和21天，每组收集3个肿瘤用于全基因表达、通路分析和免疫组织化学评估。在UT-SCC-14异种移植瘤放射治疗后的至少一个时间点，鉴定出316个与一系列干细胞相关基因相关且差异表达（p≤0.01且为1.5倍）的基因。照射后显示出显著变化的最大基因网络与CD44、NOTCH1和MET相关。c-MET和ALDH1A3染色与基因表达变化相关。出现了一种清晰的模式，与生长抑制数据一致，即与干细胞通路相关的基因在照射后第7天和第12天最为活跃。MET/CD44轴似乎是再增殖反应的一个重要组成部分。
